Radiobiological Characterization of 64CuCl2 as a Simple Tool for Prostate Cancer Theranostics
Radiobiological Characterization of 64CuCl2 as a Simple Tool for Prostate Cancer Theranostics
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DOI：
10.3390/molecules23112944
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发表时间：
2018-11-01
期刊：
影响因子：
4.6
通讯作者：
Mendes, Filipa
中科院分区：
文献类型：
--
作者：
Guerreiro, Joana Fernandes;Alves, Vitor;Mendes, Filipa
基于细胞和动物模型的临床前研究，以及越来越多的人类研究记录其用于前列腺癌诊断，(CuCl2)-Cu-64最近被认为是前列腺癌（PCa）治疗的一种有前景的药物。然而，(CuCl2)-Cu-64的使用引发了一些重要的放射生物学问题，这些问题尚未得到解决。在这项工作中，我们使用一组PCa细胞系与非肿瘤前列腺细胞系进行比较，将细胞遗传学方法与放射性细胞毒性试验相结合，以获得暴露于(CuCl2)-Cu-64的细胞后果的重要见解。发现PCa细胞表现出增加的(CuCl2)-Cu-64摄取，这不能归因于主要铜细胞进口蛋白hCtr1的表达增加，正如之前所认为的那样。前列腺癌细胞的早期DNA损伤和基因组不稳定性也更高，暴露于(CuCl2)-Cu-64后，肿瘤细胞系表现出DNA损伤修复缺陷。（CuCl2）-Cu-64在PCa细胞中的细胞毒性比在非肿瘤细胞中更强，这一点得到了证实。总的来说，我们首次发现前列腺癌细胞对(CuCl2)-Cu-64的敏感性高于健康细胞，这支持了这种化合物值得进一步评估作为前列腺癌治疗药物的观点。
(CuCl2)-Cu-64 has recently been proposed as a promising agent for prostate cancer (PCa) theranostics, based on preclinical studies in cellular and animal models, and on the increasing number of human studies documenting its use for PCa diagnosis. Nevertheless, the use of (CuCl2)-Cu-64 raises important radiobiological questions that have yet to be addressed. In this work, using a panel of PCa cell lines in comparison with a non-tumoral prostate cell line, we combined cytogenetic approaches with radiocytotoxicity assays to obtain significant insights into the cellular consequences of exposure to (CuCl2)-Cu-64. PCa cells were found to exhibit increased (CuCl2)-Cu-64 uptake, which could not be attributed to increased expression of the main copper cellular importer, hCtr1, as had been previously suggested. Early DNA damage and genomic instability were also higher in PCa cells, with the tumoral cell lines exhibiting deficient DNA-damage repair upon exposure to (CuCl2)-Cu-64. This was corroborated by the observation that (CuCl2)-Cu-64 was more cytotoxic in PCa cells than in non-tumoral cells. Overall, we showed for the first time that PCa cells had a higher sensitivity to (CuCl2)-Cu-64 than healthy cells, supporting the idea that this compound deserved to be further evaluated as a theranostic agent in PCa.